TY - JOUR
T1 - Synergy in tumor suppression by direct interaction of Neutral Endopeptidase with PTEN
AU - Sumitomo, Makoto
AU - Iwase, Akira
AU - Zheng, Rong
AU - Navarro, Daniel
AU - Kaminetzky, David
AU - Shen, Ruoqian
AU - Georgescu, Maria Magdalena
AU - Nanus, David M.
N1 - Funding Information:
The authors wish to thank Dr. Hector Casas, Jr. for technical assistance with PTEN experiments, Drs. Masamichi Hayakawa and Tomohiko Asano for useful discussions and support, and Lana Winter and Heather Orkin for secretarial assistance. These studies were supported by NIH Grant CA 80240 and the Robert H. McCooey Memorial Cancer Research Fund.
PY - 2004/1
Y1 - 2004/1
N2 - We show in this study that endogenous NEP and PTEN associate in cells directly through electrostatic interactions between a highly basic residue stretch in the intracellular domain of NEP and the major phosphorylation site in PTEN's tail. NEP binds and engages in higher order complexes both phosphorylated and unphosphorylated PTEN. NEP recruits PTEN to the plasma membrane and enhances its stability and phosphatase activity. As a result, an enzymatically inactive NEP mutant preserves the ability to bind PTEN, inactivates the Akt/PKB kinase, and partially suppresses the growth of PC cells. This study demonstrates a molecular cooperation between NEP and PTEN tumor suppressors in which NEP constitutively recruits and activates PTEN to inhibit the PI3K/Akt oncogenic pathway.
AB - We show in this study that endogenous NEP and PTEN associate in cells directly through electrostatic interactions between a highly basic residue stretch in the intracellular domain of NEP and the major phosphorylation site in PTEN's tail. NEP binds and engages in higher order complexes both phosphorylated and unphosphorylated PTEN. NEP recruits PTEN to the plasma membrane and enhances its stability and phosphatase activity. As a result, an enzymatically inactive NEP mutant preserves the ability to bind PTEN, inactivates the Akt/PKB kinase, and partially suppresses the growth of PC cells. This study demonstrates a molecular cooperation between NEP and PTEN tumor suppressors in which NEP constitutively recruits and activates PTEN to inhibit the PI3K/Akt oncogenic pathway.
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U2 - 10.1016/S1535-6108(03)00331-3
DO - 10.1016/S1535-6108(03)00331-3
M3 - Article
C2 - 14749127
AN - SCOPUS:1642512636
SN - 1535-6108
VL - 5
SP - 67
EP - 78
JO - Cancer Cell
JF - Cancer Cell
IS - 1
ER -
